Condition category
Injury, Occupational Diseases, Poisoning
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Marianne Thoresen


Contact details

School of Clinical Sciences
University of Bristol
St Michael's Hospital
Southwell Street
United Kingdom
+44 (0)117 342 5607

Additional identifiers

EudraCT number

2009-014260-19 number

Protocol/serial number

Version 1.21 (as of 05/01/2011)

Study information

Scientific title

A feasibility study of adding xenon to cooling therapy in babies at high risk of brain injury following poor condition at birth



Study hypothesis

Our experimental work has shown that by adding the inert gas xenon (50%) while undergoing hypothermia treatment the % good outcome doubles (from 35% to 70%) in both small and large survival models. This is the first clinical feasibility study combining xenon inhalation with the established neuroprotective hypothermia treatment in newborn term after moderate and severe perinatal asphyxia.

Further reading:
Dingley J, Tooley J. Porter H, Thoresen M. Xenon provides short term neuroprotection in neonatal rats when administered after hypoxia-ischemia. Stroke 2006; 37(2): 501-6.

Dingley J, Hobbs C, Ferguson J, Thoresen M. Xenon/hypothermia neuroprotection regimes in spontaneously breathing neonatal rats after hypoxic-ischemic insult: respiratory and sedative effects. Anaesthesia and Analgesia 2008; 106: 916-923.

Hobbs C, Thoresen M, Tucker AM, Aquilina K, Chakkarapani E, Dingley J. Xenon and hypothermia combine additively offering long term functional and histopathological neuroprotection after neonatal hypoxia-ischemia. Stroke 2008; 39(4): 1307-13.

Chakkarapani E, Thoresen M, Hobbs C, Aquilina K, Liu X, Dingley J. A closed-circuit neonatal xenon delivery system: technical neuroprotection feasibility study in newborn pigs. Anaesthesia and Analgesia 2009; 109(2): 451-60.

Thoresen M, Hobbs C, Wood T, Chakkarapani E, Dingley J. Cooling combined with immediate or delayed Xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. Journal of Cerebral Blood Flow and Metabolism 2009; 29(4): 707-14.

Thoresen M. Patient selection and prognostication with hypothermia treatment. Seminars in Fetal and Neonatal Medicine 2010; 15(5): 247-52

As of 01/03/2011 the target number of participants has been increased from 12 to 14

Ethics approval

North Somerset and South Bristol Research Ethics Committee approved on the 16th September 2009 (ref: 09/H0106/64)

Study design

Interventional non-randomised single centre feasibility study

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting

GP practices

Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Topic: Neurological; Subtopic: Neurological (all Subtopics); Disease: Nervous system disorders


Adding xenon to the inspiratory gas of the ventilated infant using a MHRA approved closed loop xenon-delivery system. The xenon, oxygen, carbon dioxide (CO2) and nitrogen gas concentrations are controlled.

Follow up length: 42 months
Study entry: registration only

Added 01/03/2011: The duration of treatment with Xenon gas has been increased from 12 hours to 18 hours for recruits 12, 13 and 14

Intervention type



Not Applicable

Drug names


Primary outcome measure

Physiological changes, measured within 24 hours after end treatment

Secondary outcome measures

1. Bayley III, measured at 18 or 24 months
2. MRI, measured within 14 days after treatment

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Infants will be eligible for xenon if the St Michael's standard inclusion criteria for cooling are met. Standard Hypothermia Treatment Criteria for 72 hours of cooling - all of criteria A, B, and C:

A: Infants greater than 36.0 weeks gestation (clinical assessment) with at least one of the following:
1. Apgar score of less than 5 at ten (10) minutes after birth
2. Continued need for resuscitation, including endotracheal or mask ventilation, at ten minutes after birth
3. Acidosis defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less than pH 7.00
4. Base deficit greater than or equal to 16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood)
If the infant meets criterion A then assess for neurological abnormality using criterion B and C (by trained personnel).

B: Moderate or severe encephalopathy as evidenced by:
1. Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive
And at least one or more of the following:
2. Hypotonia
3. Abnormal reflexes including oculomotor or pupillary abnormalities
4. Absent or weak suck
5. Clinical seizures, as recorded by trained personnel

C: At least 30 minutes duration of amplitude integrated electroencephalography (aEEG) recording that shows abnormal background aEEG activity. The decision to cool is based on the worst section of the aEEG, not the best (al Naqeeb, et al, 1999) or seizures (clinical or electrical) thus meeting ONE of the following:
1. Normal background with some electrical seizure activity
2. Moderately abnormal activity (upper margin of trace greater than 10 µV and lower margin less than 5 µV)
3. Suppressed activity (upper margin of trace less than 10 µV and lower margin of trace less than 5 µV)
4. Definite seizure activity

Additional inclusion criteria for xenon:
Before being considered for additional inhaled xenon therapy via the breathing gas mixture, the infant would need to meet further additional entry criteria:
1. Intubated, ventilated, sedated, being cooled
2. Any seizures under control
3. Weight greater than 2.3 kg
4. No evidence of infection
5. Stable cardiovascular parameters - mean arterial pressure greater than 45mmHg
6. Oxygen requirement via mechanical ventilator less than 35%
7. Positive end expiratory pressure (PEEP) requirement less than 6 mmHg
8. Arterial pCO2 within the accepted range (4.5 - 6.5 kPa)
9. Postnatal age less than 18 hours, either sex
10. Major congenital abnormalities, imperforate anus and congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis

Participant type


Age group




Target number of participants

Added 01/03/2011: 14 (12 at time of registration)

Participant exclusion criteria

1. Infants expected to be greater than 12 hours of age at the time of starting cooling treatment
2. Futility; where prognosis is considered to be hopeless, e.g. no cardiac output for 20 minutes
3. Failure to meet the additional inclusion criteria for xenon

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

School of Clinical Sciences
United Kingdom

Sponsor information


University Hospitals Bristol NHS Foundation Trust (UK)

Sponsor details

Research and Development
Upper Maudlin Street
United Kingdom
+44 (0)117 342 0233

Sponsor type




Funder type


Funder name

Sparks (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2014 results in:

Publication citations

Additional files

Editorial Notes